This invention relates to a method of forming a radiant energy-generated, permanent three-dimensional polymeric image in a gel and to an article of manufacture comprising a gel adapted for use as a dosimeter, e.g., of ionizing radiation.
There are numerous applications for a dosimetric technique that can accurately measure radiation dose distributions in three dimensions with high spatial resolution. For example, in radiation therapy there are several treatment regimes for which it would be valuable to characterize the distribution of radiation with millimeter resolution in tissue-equivalent, homogeneous and heterogeneous media. Towards this end, the use of aqueous gels containing Fricke dosimeter solution in combination with magnetic resonance imaging (MRI) techniques was suggested. See Gore, J. C., et al., Phys. Med. Biol. 29:1189-1197; 1984; Abstract. Res. Imaging 2:244; 1984.
It was shown that the radiation-induced oxidation of ferrous ions to ferric in solution could be detected by a change in the water proton spin relaxation times, T1 and T2, and the changes were large enough to be mapped with high spatial resolution by magnetic resonance imaging (MRI) when the Fricke solution was dispersed in a gelatin or agarose gel. Gore, J. C., et al., Mag. Res. Imaging, supra; Schulz, R. J., et al., Phys. Med. Biol. 35:1611-1622; 1990.
The conversion of ferrous to ferric ions promotes proton relaxation because the ferric ions produce stronger paramagnetic dipole-dipole interactions with the water protons. Also, the water relaxation rates are proportional to radiation dose over a wide range of doses. This work promoted several groups to investigate this approach to radiation dosimetry. Day, J. J. Phys. Med. 35:1605-1609; 1990; Olsson, L. E., Ph.D. Thesis, Lund University, Malmo, Sweden, 1991.
Their results verify the potential value of such an imaging technique. For example, the practical value and unique ability of this technique to map the dose distributions of the complex irradiations used in stereotactic radiosurgery have recently been demonstrated. Olsson, L. E., supra; Schultz, R. J., et al., "Assessment of the accuracy of stereotactic radiosurgery using Fricke-infused gels and MRI" (Unpub., submitted to Med. Phys.). However, there is a major disadvantage that is intrinsic to the Fricke gel medium, viz., ferric ions are able to diffuse quite freely through the gel after irradiation, with a point spread function whose width is about 2 mm after one hour. Schulz et al., supra; Olsson, L. E., supra. This leads to a gradual blurring of the radiation dose pattern and a consequent loss of spatial resolution, and places constraints on the minimum dose rate that can be applied, on the time between irradiation and imaging, and on a number of images that can be recorded before diffusion introduces errors in the subsequent calculation of relaxation times. There are ways to correct for this diffusion but the complexities of this approach present a major limitation to the practicality of the technique. A gel in which diffusion of, the radiation-induced, NMR-sensitive species is insignificant over relatively long periods of time would be highly advantageous, especially when weak radioactive brachytherapy sources are to be studied.
Other dosimetry systems employing gels or polymerizable resins are described in the patent literature. U.S. Pat. No. 4,430,258 discloses a method of producing liquid equivalent solid gamma ray calibration standards comprising the steps of adding a first organic solvent to a calibrated aqueous solution of radioactive material, either in the form of a single isotope or mixed isotopes, to form a first solution; mixing the first solution with a polymerizable resin dissolved in a second organic solvent together with a hardening catalyst to form a second solution; and curing the second solution. With isotope standards requiring highly acidic conditions, a stabilizing agent is added to the first solvent to complex with metal and hydrogen ions so as to prevent plate-out.
U.S. Pat. No. 4,588,698 discloses microencapsulation of solid phase scintillators in gels selectively permeable to diffusible radioactive label. These encapsulated scintillators are used to monitor the concentration of radioactive-tagged substances in fluid systems.
U.S. Pat. No. 4,350,607 discloses a radiation detector and dosimeter which is based on the fact that a sufficiently finely-dispersed liquid suspended in a host liquid of high viscosity or gel is stable at temperatures above its normal boiling point for long periods of times provided it is protected from contact with walls, or other types of initiators which can cause volatilization or vaporization of the droplets. Radiation, and particularly neutron radiation of sufficient energy and intensity on coming in contact with such droplets can trigger volatilization. The volume of vapor evolved then serves as a measure of radiation intensity and dosage.
U.S. Pat. No. 4,779,000 discloses a direct reading, self-powered detector and dosimeter for gamma rays, and other low LET radiation, and optionally microwaves in which a transparent elastic solid medium contains uniformly dispersed droplets of a very high vapor pressure detector liquid substantially immiscible with the elastic solid. It has been found possible to form stable droplets having a sufficiently high degree of superheat for their vaporization to be sensitive to lightly ionizing radiation such as gamma rays and even to microwave radiation. The solid medium will retain a record of each droplet vaporized, the number being proportional to the dose of radiation. If desired, the detector liquid vapors can be condensed or compressed into droplets again and the detector/dosimeter re-used.
U.S. Pat. No. 4,946,705 discloses a device for measuring gaseous substances which comprises a reflectant backing which is disposed a layer which is composed of microparticles coated with a reagent and then with a diffusion layer which contains a diffusion moderator, viz., a film forming high molecular weight material and binder, and optionally a plasticizer.
U.S. Pat. No. 3,616,369 discloses a method for controlling the molecular weight of a polymer derived from an ethylenically unsaturated monomer which can be catalyzed to polymerize by a Lewis acid, which comprises mixing said monomer with a Lewis base soluble in the monomer, and then reacting the mixture with an amount of high-energy radiation at least sufficient to initiate and propagate polymerization of the monomer, the Lewis base being selected from the class which functions to determine the molecular weight of the polymer produced at a given radiation dosage and temperature; the monomer being selected from ethylenically unsaturated monomers having electron-releasing groups attached directly or indirectly to the ethylenic linkage of the monomer which impart a Lewis base character to said monomer.
The invention is said to be also applicable to controlling the molecular weight of a polymer derived from a monomer which can be catalyzed by a Lewis base by mixing the monomer with a Lewis acid and then irradiating the mixture at a given temperature and to a given radiation dosage.
The following patents relate to a process of building a three-dimensional object by adding layer upon layer (laminations) using some form of energy beam (light, ionizing radiation, etc.) controlled by a computer program on a polymerizing medium: U.S. Pat. Nos. 5,130,065; 5,123,734; 5,104,592; 5,096,530; 5,076,974; 5,059,359; 5,059,021; 5,058,988; 5,015,424; 4,999,143; 4,996,010; 4,929,402; and 4,575,330.